Respiratory Abnormalities in Parkinson’s Disease: What Do We Know from Studies in Humans and Animal Models?

Abstract

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease characterized by movement disorders due to the progressive loss of dopaminergic neurons in the ventrolateral region of the substantia nigra pars compacta (SNpc). Apart from the cardinal motor symptoms such as rigidity and bradykinesia, non-motor symptoms including those associated with respiratory dysfunction are of increasing interest. Not only can they impair the patients’ quality of life but they also can cause aspiration pneumonia, which is the leading cause of death among PD patients. This narrative review attempts to summarize the existing literature on respiratory impairments reported in human studies, as well as what is newly known from studies in animal models of the disease. Discussed are not only respiratory muscle dysfunction, apnea, and dyspnea, but also altered central respiratory control, responses to hypercapnia and hypoxia, and how they are affected by the pharmacological treatment of PD.

A systematic review and meta‐analysis of respiratory dysfunction in Parkinson's disease

“…In all studies, except one, RRs observed were above the normal adult range and between 1 and 6 bpm higher than controls; however, they remained within rates reported in older adults without respiratory complications 75, 76 . High heterogeneity and relatively small numbers observed may limit meaningful interpretation of RR findings which differ from animal studies in PD where basal RR during daytime is reduced 18, 21, 78–81 . One explanation may be the prevalence of levodopa‐induced dyskinesia during the ON phase of medication causing an increased and irregular RR 82 .…”

“…A consistent finding across the narrative reviews conducted to date is the presence of multiple, conflicting reports of respiratory dysfunction in PD 18–21 . To date, no study has summarised what is currently known and has been measured in respiratory function in individuals with PD.…”

“…Medications are proposed to have positive and negative effects on respiratory function, by improving muscle co‐ordination and maintaining inspiratory muscle strength, but also causing side effects including stridor and diaphragmatic dyskinesia 22, 24, 25, 27, 28 . Central mechanisms focus on brain and brain stem respiratory control centre changes, with clinical signs including dyspnoea, sleep apnoea and pneumonia 18–21 . Impaired chemosensitivity has been proposed as another mechanism warranting consideration 29, 30 .…”

“…[14][15][16] Despite James Parkinson noting in 1817 "…he fetched his breath rather hard…", indicating easily observed clinical features of respiratory dysfunction in PD, 17 the aetiology of this dysfunction remains unclear to this day. [18][19][20][21] Mechanisms for respiratory deficits in PD have been proposed in recent narrative reviews and include both peripheral and central systems. [18][19][20] Peripheral mechanisms include restrictive dysfunction, obstructive dysfunction and adverse effects of PD medications.…”

“…22,24,25,27,28 Central mechanisms focus on brain and brain stem respiratory control centre changes, with clinical signs including dyspnoea, sleep apnoea and pneumonia. [18][19][20][21] Impaired chemosensitivity has been proposed as another mechanism warranting consideration. 29,30 Changes in central ventilatory control, presenting as abnormal perception of dyspnoea, link to the recognition of brainstem involvement in early, premotor impairment stages of PD.…”